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The transcription factor <jats:italic>WT1<\/jats:italic>\u00a0has long been reported to play a crucial role in ovary function. <jats:italic>Wt1<\/jats:italic>\u2010mutated female mice exhibited POI\u2010like phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>In this study, whole exome sequencing (WES) was applied to find the cause of POI in Han Chinese women. A nonsense variant in the <jats:italic>WT1<\/jats:italic>\u00a0gene: NM_024426.6:c.1387C&gt;T(p.R463*) was identified in a non\u2010syndromic POI woman. The variant is a heterozygous de novo mutation that is very rare in the human population. The son of the patient inherited the mutation and developed Wilms\u2019 tumor and urethral malformation at the age of 7. According to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG\/AMP) guidelines, the novel variant is categorized as pathogenic. Western blot analysis further demonstrated that the <jats:italic>WT1<\/jats:italic> variant could produce a truncated WT1 isoform in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A rare heterozygous nonsense <jats:italic>WT1<\/jats:italic>\u00a0mutant is associated with non\u2010syndromic POI and Wilms\u2019 tumor. Our finding characterized another pathogenic <jats:italic>WT1<\/jats:italic> variant, providing insight into genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1820","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T16:35:23Z","timestamp":1638290123000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Whole exome sequencing identified a rare <i>WT1<\/i> loss\u2010of\u2010function variant in a non\u2010syndromic POI patient"],"prefix":"10.1002","volume":"10","author":[{"given":"Yingchen","family":"Wang","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Hospital NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research) School of Life Sciences Fudan University Shanghai 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